The core will function as a shared resource for this program project. The objective of the core is the large scale production of helper-dependent adenoviral vectors for testing in small animal and nonhuman primate studies. The high cost of the infrastructure and expertise necessary to produce a large quantity of helper-dependent adenoviral vectors necessitate a vector production core having this function. The physical characteristics of the facility will help assure replication competent adenovirus-free vector production. These include design of cell culture room, biosafety hoods, and physical separation of incubators for high titer virus from low titer virus production. Equipment and supplies approved for the production of biological used in preclinical studies will be used at the facility. This includes certification by the suppliers, quality assurance by the facility, and standard operating procedures for the receipt, inventory, expiration and disposal of all material. The core will be responsible for the production of a master cell bank and a working cell bank necessary for the production of the vectors at sufficient scale under controlled conditions to allow their use in laboratory animals in vivo. In the core laboratory, rescued adenoviral vectors will be serially passaged in helper virus (AdLC8cluc) infected 293 cells that stably express the Cre recombinase (293Cre4 cells) to produce high titer virus. The core will be also responsible for producing sufficient helper virus for the entire operation. High quality adenoviral vectors will be prepared by cesium chloride density gradient ultracentrifugation to separate adenoviral vectors from contaminating helper virus. The core will exercise tight quality control to ensure the safety of the materials that will be administered and to ensure the safety of the personnel involved in the production of the vectors. This will involve detailed record keeping, in- house quality assurance and the oversight of quality control tests. The core director of the laboratory will be responsible for personnel training and compliance with all requirements for adenovirus production.